In some species of primates as well as guinea pigs, infants exhibit a 2 -stage, active /passive response during maternal separation. The second stage (termed "despair" in primates) of separation from the maternal attachment figure has been a long-standing model for the study of depressive illness. It recently has been hypothesized that behaviors that guinea pig pups show during the passive stage represent "stress- induced sickness behaviors" (i.e., components of a systemic inflammatory or acute phase, response that can be elicited by stressors as well as immunological stimuli.) Studies proposed here would further test this hypothesis (Specific Aim 1) by determining if the passive responses and increased core temperature (a . physiological indicator of the acute phase response) that have been observed in separated guinea pig pups can be reversed by central administration of the anti-inflammatory agents alpha -MSH and lnterleukin-10 (IL- 10), by determining if the minimum effective dose of alpha MSH and IL-10 can reverse frank sickness behaviors induced by lipopolysacchride, and by examining whether alpha MSH and IL-10 produce increases in endogenous IL-10 mRNA. Specific Aim 2 is to begin to evaluate the feasibility of the model for the study of depression (specifically as an animal model for the cytokine hypothesis of depression) by determining whether chronic fluoxetine and desipramine exposure can reduce the putative stress-induced sickness responses and temperature elevations during separation, and increase activity of IL-10. The proposed work meets the objectives of the AREA mechanism by providing meaningful research experience to undergraduates. Further, this research addresses several priorities for NIMH research listed by the NAMHC Workshop on the Basic Sciences of Mental Health in 2003, specifically: three areas identified for increased emphasis (emotion, development, and social interactions), one type of identified needed research tool (animal model) and one area identified for refocus (stress). The relevance of the work is that it would: (1) provide new information on the way in which the brain, endocrine, and immune systems can interact to produce potentially pathological behavioral changes; and, (2) begin to realign a long-standing animal model of depression with current views of depressive illness. [unreadable] [unreadable] [unreadable]